ABSTRACT/PROJECT SUMMARY FOR SUPPLEMENT Agitation is common in Alzheimer's disease (AD), and a major burden to patients and caregivers. Finding effective treatments is a priority. This approach has several challenges in the real world including unknown efficacy, sparse use of non-pharmacologic therapies, and widespread, often inappropriate, use of antipsychotics that carry significant risks. There is need for effective therapies for agitation combining non-pharmacologic with novel pharmacologic approaches, reducing antipsychotic use, and targeting therapies to appropriate subgroups of this heterogeneous condition. Attempting to develop a novel therapy targeting the serotonin system, we conducted Citalopram in AD (CitAD). In CitAD, racemic citalopram was effective for agitation with 40% of citalopram-treated participants experiencing substantial clinical improvement vs. only 26% on placebo. However, citalopram was associated with cognitive worsening and prolongation of the ECG-QTc interval. In blood concentration models, cognitive and cardiac changes were associated with the R-enantiomer, while clinical improvements were primarily associated with the S-enantiomer (escitalopram). We have implemented S-CitAD to build on and extend these findings. We will evaluate the efficacy of an evidence-based, sequential approach to treating agitation in AD with real world applicability for patients. In this supplement we propose to add actigraphy to enhance the aims of the parent study S- CitAD. We will perform actigraphy twice: between the enrollment and baseline visit, and between week 9 and week 12 visits. We propose to use actigraphy as an objective measure of activity and agitation to enhance the parent trial's subjective measures. IMPACT: Actigraphy will allow for objective measurement of agitation to reinforce and enhance the parent trial's aims.